Objective To study the changes of negative symptoms in PCP-induced schizophrenia rat model.Methods Thirty newborn female SD rats randomly divided into control group,PCP-week 6 group and PCP-week 10 group( n=10 in each group).Perinatal rat treated with PCP ( 10 mg/kg) on postnatal days 7,9 and 11(10 mg/kg,ip),and sucorse intalce test(SIT),forced swimming test(FST) and resident-intruder test(RIT) were used to test the emotional and negative symptoms.Results In the SIT,there was no difference between control and PCP groups (con:(28.24 ±0.86) ml/kg; week 6:(26.57 ± 1.01 ) ml/kg; week 10:(27.98 ±0.99) ml/kg,F =12.35,P ＞ 0.05 ).In the FST,PCP model rats showed longer still time ( con:(39.32 ± 1.98 ) s ; week 6:(52.39 ± 1.66)s,week 10:(55.56 ± 1.49)s,F=3.99,P＜ 0.05 ).In the RIT,PCP models rats showed less explore time ( (40.31 ± 13.56)s vs (63.90 ± 13.12)s,(43.65 ±12.86 )s vs (65.18 ± 15.12)s,P ＜ 0.05 ) and more escape time ((19.33±2.26) s vs (9.26 ± 1.32) s,(17.79 ±2.99) s vs (9.38 ± 1.36) s,P＜ 0.05).Conclusion Perinatal PCP injection can induce the long-lasting negative-symptoms changes.

Objective To investigate the protective effects and underlying mechanisms of Liuwei Dihuang Glucoside(LW-AFC)against fear sensitization induced by traumatic stress.Methods Mice were divided into naive,control,stressed and LW-AFC administration groups.The LW-AFC treated group received LW-AFC(1.6 g/kg daily)via oral gavage for two weeks following exposure to traumatic stress.The non-associative memory dependent fear sensitization responses in mice subjected to trauma were investigated,including behavior in novel environments,social interaction,and observational fear tests.Z-score normalization method was employed to integrate and assess multiple behavioral variables such as travel distance,freezing time,and corner time,and comprehensively examined fear sensitization behaviors across the groups.Additionally,serum concentrations of adrenocorticotropic hormone,corticosterone,aldosterone,renin,angiotensin Ⅱ,and aldosterone were measured using ELISA.Results Compared to the control group,stressed mice exhibited significantly reduced travel distance(P<0.0001)and increased freezing time(P<0.0001)in the new context test.Integrated Z-scores indicated a significant increase in fear behavior among stressed mice during the new context test(P<0.0001).In the social interaction test,stressed mice demonstrated significantly reduced travel distance(P<0.0001),increased freezing time(P<0.0001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).In the observational fear test,stressed mice showed significantly reduced travel distance(P<0.05),increased freezing time(P<0.001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).Compared to the stressed group,mice in the LW-AFC treated group displayed trends toward improvement in travel distance,freezing time,corner time,and integrated Z-scores in the new context tests,albeit without statistical significance.In the social interaction test,the LW-AFC treated group exhibited a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.05).In the observational fear test,the LW-AFC treated group showed a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.01).Compared to the naive group,control and stressed groups exhibited an increased trend in renin and aldosterone levels after the fear sensitization test.Although there were no significant differences between stressed and control groups,renin and aldosterone levels significantly increased between stressed and naive groups(P<0.05,P<0.05).Following LW-AFC treatment,serum renin levels showed no significant change,while aldosterone levels significantly decreased(P<0.05).Conclusion Stressed mice exhibited significant fear sensitization behavior in new context,social interaction,and observational fear tests,possibly associated with partial activation of the renin-angiotensin-aldosterone system(RAAS)system.LW-AFC treatment significantly mitigated fear sensitization behavior of stressed mice in social interaction and observational fear test,potentially due to its regulatory effects on the RAAS system in mice subjected to traumatic stress.

OBJECTIVE Human beings possess the ability to indirectly acquire the emotions of others.This also known as emotional contagion or empathy,enables us to rapidly perceive the emotions of others.However,an excessive empathy may result in heightened fear and sensitivity to pain.Therefore,the establishment of appropri-ate animal models for analyzing neural mechanisms underlying empathy would contribute to pharmacological research on pain sensitivity caused by psychological sus-ceptibility.METHODS We used the observed fear para-digm for assessing contagion of negative emotions in mice.To minimize the impact of emotional contagion dif-ferences caused by the subject change,we established a bilateral observation area and the two mice were trained to observe fear simultaneously.First,two observer(OB)mice were placed on either side of the observational area.Next,a demonstrator(DM)mouse was introduced into the cylindrical shock cage located at the center of the apparatus.The shock cage is made of transparent organic plastic with air holes and has provided ample space for free movement by the DM mouse.During the shock stage,DM mice were subjected to electric stimulation while the behaviors of OB mice on both sides was observed,including freezing,the side and corner time,social interaction behavior.Additionally,c-Fos staining was utilized to confirm distinct local brain activities.RESULTS In the habituation stage,OB mice on both sides showed more social preference for DM mouse,as evidenced by an increase in duration time in the designat-ed interaction zone.During the shock phase,OB mice observed the DM mouse receiving electric shocks and displayed significantly higher levels of fear contagion;however,their fear behavior was not entirely consistent.Some mice exhibited a significant increase in freezing time,while others demonstrated a significant increase in corner and side exploration time.We utilized Z-normal-ization to evaluate changes in emotionality across vari-ous behaviors and identified mice with distinct susceptibil-ities.Fos-positive neurons exhibited higher expression levels in susceptible OB mice,primarily concentrated within brain regions associated with the ascending path-ways of pain perception,such as thalamus,the anterior insular cortex,and anterior cingulate cortex.CONCLU-SION In this study,we have developed an innovative experimental facility that integrates various behavioral tests to evaluate empathic behavior in mice.Our findings highlight the robustness of emotionality measures obtained from individual mice by combining this experi-mental model with the Z-scoring method,facilitating screening for empathic fear or pain-susceptible mice and will helpful for pharmacological evaluation.

OBJECTIVE Fear can be learned indi-rectly,but excessive transmission of fear is essential for the development of mental illness.Previous research has indicated that the anterior insular cortex(AIC)may play a crucial role in the process of fear transmission,and abnormal AIC activity is a possible mechanism under-lying various affective disorders.Inhibitory neurons are crucial for maintaining local microcircuit homeostasis.With the support of novel specific neuroregulatory tech-niques,it is now possible to monitor and regulate differ-ent types of neurons in real-time.Therefore,investigating distinct subtypes of inhibitory neurons in the AIC that are involved in fear contagion may provide valuable insights into potential mechanisms underlying mental disorders.METHODS We established a modified observational fear(OF)model.A demonstrator(DM)mouse was placed in an acrylic cup at the center of the apparatus,and two observer(OB)mice were allowed to explore the DM mouse simultaneously from separate areas on either side.During the OF training,electric foot shocks were administered to the DM mouse and freezing,the side and corner time,and social interaction behavior were scored.Next,we characterized the activity patterns of distinct neuronal subtypes in the AIC using GCaMP-based calcium recording.Finally,we employed a Cre-dependent optogenetic approach to selectively modulate excitatory or inhibitory neurons in the AIC,and investigat-ed empathic fear behavior across different Cre transgenic mouse lines(CK2-Cre,PV-Cre,SOM-Cre,VIP-Cre).RESULTS During the training phase,the OB mice exhib-ited significantly higher levels of fear compared to the control group(which did not observe a traumatic event),as evidenced by increased freezing time,decreased interaction time,and increased corner zone time.Calcium fiber recording results suggested that CK2 neurons are involved in risk prediction,while PV and VIP neurons exert inhibitory control on this behavior.Optogenetic silencing of CK2-positive neurons in the AIC through injection of AAV-DIO-NpHR-mCherry in mice demon-strated a significant reduction in empathic fear.Similarly,activation of PV or VIP inhibitory neurons expressing ChR2-eYFP also resulted in a similar effect.However,activation of SOM neurons led to a significant increase in empathic fear.CONCLUSION Our study demonstrated that VIP and PV neuron activity in the AIC attenuates empathetic fear,while SOM and CK2 neuron activity enhances fear expression.These findings shed light on the distinct contributions of various inhibitory interneu-rons in the AIC to fear contagion,indicating their mutual interaction for maintaining local microcircuit homeostasis that regulates empathetic fear behaviors.